Authors: Liadet L, Szabo C

DOI:10.1186/s13054-020-03055-6

Abstract

The pulmonary renin angiotensin (Ang) system (RAS) comprises two pathways whose balance is important for lung homeostasis. Endothelial ACE generates Ang II, acting on AT1 receptors to promote vasoconstriction and pro-inflammatory effects, whereas epithelial ACE2 cleaves Ang II into Ang1–7, acting on the Mas receptor to exert vasodilatory and anti-inflammatory effects. A shift towards predominant ACE-dependent Ang II formation has been postulated as an important pathophysiological mechanism in various forms of ARDS.SARS-CoV-2 uses lung ACE2 as its cellular receptor, resulting in ACE2 degradation and ACE/ACE2 imbalance, which could drive Ang II-mediated vascular inflammation and lung injury in severe COVID-19 disease. Furthermore, Ang II induces the release of aldosterone, which can promote further vascular damage via mineralocorticoid receptor (MR) activation. Aldosterone also exerts multiple actions on immune cells, which express the MR. MR activation polarizes macrophages towards the M1 pro-inflammatory phenotype. In lymphocytes, MR activation promotes the differentiation of pro-inflammatory Th17 CD4+ cells and of cytotoxic IFNγ+-CD8+ T cells, indicating that MR activation in immune cells promotes a hyperinflammatory profile. It is particularly noticeable that Th17 T cells increase and high CD8+ cells cytotoxicity have been proposed to be involved in the hyperinflammatory state characterizing COVID-19 ARDS.

Keywords: mineralocorticoid receptor, spironolactone, COVID-19, SARS-CoV2

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